ABCG2PolymorphismsMDR1SubstratesCYP3A4Multidrug resistanceCYP3A5C3435TATPaseSubstrateTransporterSNPsSignificantlyPaclitaxelProtein expressionOverexpressionVariantsMicroRNAsEncodesChemotherapeuticPlasma concentrationsInterestinglyDoxorubicinDonorSpeciesCorrelationInteractionContrastCancerDrugCellsEffectsCell
ABCG221
- Here, we investigated that cetuximab, an EGFR monoclonal antibody, reversed the chemoresistance mediated by ABCB1, ABCG2 or ABCC1. (oncotarget.com)
- Our results showed that cetuximab significantly enhanced the cytotoxicity of ABCB1 substrate agent in ABCB1-overexpressing MDR cells but had no effect in their parental drug sensitive cells and ABCC1, ABCG2 overexpressing cells. (oncotarget.com)
- Molecular aspects of ABCB1 and ABCG2 in Gallbladder cancer and. (mysciencework.com)
- Among the main mechanisms of this multidrug resistance is the overexpression of ATP-binding cassette (ABC) transporters that mediate drug efflux, and, specifically, ABCB1, ABCG2 and ABCC1 are known to cause cancer chemoresistance. (nature.com)
- In this Review, we highlight the progress achieved in the past 5 years on the three transporters, ABCB1, ABCG2 and ABCC1, that are known to be of clinical importance. (nature.com)
- Fig. 1: Selected substrates transported by ABCB1, ABCG2 and ABCC1. (nature.com)
- Superior Pyrimidine Derivatives as Selective ABCG2 Inhibitors and Broad-Spectrum ABCB1, ABCC1, and ABCG2 Antagonists. (bvsalud.org)
- Furthermore, 11 pyrimidines were revealed as triple ABCB1/ABCC1/ABCG2 inhibitors. (bvsalud.org)
- The most promising representative, compound 37, reversed ABCB1-, ABCC1-, and ABCG2-mediated MDR, making it one of the three most potent ABC transporter inhibitors and reversers of ABC transporters -mediated MDR. (bvsalud.org)
- The cytotoxic activity of OTS964 was limited in B1/G2 cells relative to that in parental PEL cells, and that this effect can be partially re-sensitized by a known inhibitor of ABCB1 or ABCG2. (biomedcentral.com)
- Association between ABCB1, ABCG2 carrier. (bezmialem.edu.tr)
- Common variants in ABCB1, ABCC2 and ABCG2 genes and clinical outcomes " by Christine B. Ambrosone, Kathleen M. Darcy et al. (gwu.edu)
- Common variants in ABCB1, ABCC2 and ABCG2 genes and clinical outcomes among women with advanced stage ovarian cancer treated with platinum and taxane-based chemotherapy: A Gynecologic Oncology Group study. (gwu.edu)
- The present study was aimed to evaluate the possible effects of ABCB1 C3435T and ABCG2 C421A single nucleotide polymorphisms on clinical and pathological outcomes of Kurdish patients with breast cancer. (ac.ir)
- The ABCB1 C3435T and ABCG2 C421 genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP). (ac.ir)
- There was no statistically significant association between ABCB1 C3435T and ABCG2 C421A polymorphisms and tissue expression of ER, PR, Her2/neu, and Ki67. (ac.ir)
- Colocalized in membrane barriers, the ABC transporters ABCB1 and ABCG2 strongly contribute to multidrug resistance (MDR). (unibas.ch)
- For this purpose we measured the ATPase activity of ABCG2 and ABCB1 as a function of allocrite concentration using a calibration set of 30 diverse compounds and a validation set of 23 compounds. (unibas.ch)
- The concentrations of half-maximum activation and inhibition are at least 10-fold lower for ABCG2 than for ABCB1. (unibas.ch)
- Because ABCG2 binds its allocrites with higher affinity than ABCB1, it can extract hydrophilic, nonamphiphilic, and highly charged compounds out of the lipid membrane, typically exhibiting low lipid-water partition coefficients, but is inhibited by hydrophobic, amphiphilic, and moderately charged compounds, with high lipid-water partition coefficients. (unibas.ch)
- Parameters reflecting hydrophobicity, amphiphilicity, and charge are therefore sufficient for differentiating between allocrites, activators, and inhibitors of ABCB1 and ABCG2. (unibas.ch)
Polymorphisms7
- Influence of ABCB1, CYP3A5 and CYP3A4 gene polymorphisms on. (lww.com)
- ABCB1 polymorphisms are associated with clozapine plasma levels in psychotic patients. (univpm.it)
- Therefore, the aim of the present study was to investigate the possible association between ABCB1 polymorphisms and clozapine plasma levels in psychotic patients. (univpm.it)
- A 2015 review of polymorphisms in ABCB1 found that "the effect of ABCB1 variation on P-glycoprotein expression (messenger RNA and protein expression) and/or activity in various tissues (e.g. the liver, gut and heart) appears to be small. (wikipedia.org)
- Although polymorphisms and haplotypes of ABCB1 have been associated with alterations in drug disposition and drug response, including adverse events with various ABCB1 substrates in different ethnic populations, the results have been majorly conflicting, with limited clinical relevance. (wikipedia.org)
- Intracellular accumulation of atazanavir/ritonavir according to plasma concentrations and OATP1B1, ABCB1 and PXR genetic polymorphisms. (unito.it)
- Single nucleotide polymorphisms (SNPs) in genes encoding TAC metabolizing enzymes cytochromes P450 3A4/5 (CYP3A4/5), P-glycoprotein efflux transporter (ABCB1), their expression regulator pregnane X receptor (NR1I2) and CYP3A co-factor cytochrome P450 reductase (POR) have been studied for their effects on tacrolimus disposition. (edu.au)
MDR15
- P-glycoprotein 1 (permeability glycoprotein, abbreviated as P-gp or Pgp) also known as multidrug resistance protein 1 (MDR1) or ATP-binding cassette sub-family B member 1 (ABCB1) or cluster of differentiation 243 (CD243) is an important protein of the cell membrane that pumps many foreign substances out of cells. (wikipedia.org)
- ABCB1 encodes a multi-drug-resistance gene ( MDR1 ), and is the most prominent member of the ABC transporter family, and it is the most thoroughly investigated member of this family [ 9 ]. (biomedcentral.com)
- To study this vectorial transport of organic cations, we constructed a double-transfected Madin-Darby canine kidney strain II (MDCKII) cell line permanently expressing the human organic cation transporter 1 (OCT1, SLC22A1) in the basolateral membrane and MDR1 P-glycoprotein (MDR1 P-gp, ABCB1), an adenosine triphosphate (ATP)-dependent efflux pump for organic cations, in the apical membrane. (nih.gov)
- rs2235040 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein that transports certain molecules across the blood-brain barrier. (snpedia.com)
- The UIC2 monoclonal antibody specifically binds to an extracellular epitope of CD243, which is also known as ATP-binding cassette subfamily B member 1 (ABCB1), Multidrug resistance protein 1 (MDR1), or P-glycoprotein 1. (bdbiosciences.com)
Substrates2
- In this view, changes in the pharmacokinetics of drugs that are ABCB1 substrates could be clinically relevant and the evaluation of ABCB1 SNPs should deserve particular attention. (univpm.it)
- 10.1016/j.neuron.2007.11.017 found that rs2235040 (A) carriers treated with ABCB1 substrates were more likely to remit. (snpedia.com)
CYP3A41
- The study of ABCB1 and CYP3A4/3A5 gene polymorphism genes is promising in terms of their influence on prothrombin time variability, the residual equilibrium concentration of direct oral anticoagulants (DOACs) in patients with atrial fibrillation and the development of new personalized approaches to anticoagulation therapy in these patients. (lww.com)
Multidrug resistance1
- Our findings include compounds that killed by inducing phosphodiesterase 3A-Schlafen 12 complex formation, vanadium-containing compounds whose killing depended on the sulfate transporter SLC26A2, the alcohol dependence drug disulfiram, which killed cells with low expression of metallothioneins, and the anti-inflammatory drug tepoxalin, which killed via the multidrug resistance protein ATP-binding cassette subfamily B member 1 (ABCB1). (nature.com)
CYP3A52
- We suggest that ABCB1, but not CYP3A5, may predict short-term remission of Tac in steroid-refractory UC. (uni-luebeck.de)
- It was observed that CYP3A5 expressors (*1/*1 + *1/*3) (p = 5.5 × 10⁻¹⁶ ) and ABCB1 61G allele carriers (p = 0.001) had lower log-transformed TAC C₀/D (56% and 26% lower geometric mean TAC C₀/D, respectively) and accounted for approximately 30% and 4%, respectively, of log-transformed TAC C₀/D variability in the first 3 months post-transplant. (edu.au)
C3435T1
- The ABCB1 C3435T has no correlation with clinical findings and treatment with chemotherapy drugs. (ac.ir)
ATPase5
- Cetuximab stimulated the ATPase activity but did not alter the expression level of ABCB1 or block phosphorylation of AKT and ERK. (oncotarget.com)
- OTS964 stimulated ATPase activity of ABCB1 and upregulated expression levels of ABCB1, resulting in induced resistance to other ABCB1 substrate-drugs, such as paclitaxel. (biomedcentral.com)
- G Effects of OTS964 on ATPase activity mediated by ABCB1. (biomedcentral.com)
- Effects of 0-40 μM OTS964 with or without 1 μM tepotinib on ATPase activity of ABCB1. (biomedcentral.com)
- Concentration of OTS964 was plotted against basal level (without OTS964) of ABCB1 ATPase activity. (biomedcentral.com)
Substrate5
- OTS964 received a comparable affinity score and can dock into the substrate-binding site of human ABCB1 protein. (biomedcentral.com)
- Meanwhile, doxorubicin (DOX), a verified ABCB1 substrate, was used as a reference to compare the degree of reduced efficacy caused by ABCB1-overexpressing (Fig. S 1 and Table S 1 -S 2 ). (biomedcentral.com)
- H - J Highest-scoring docked pose of OTS964 within human ABCB1 at substrate-binding site. (biomedcentral.com)
- However, this result failed to reproduce in a large (900 outpatient subjects) and better designed double-blind study of a well-researched ABCB1 substrate citalopram in depression (STAR-D study). (snpedia.com)
- Other results from [ PMID 25487678 ] are unreliable because the authors used an antidepressant sertraline, which is, likely, not an ABCB1 substrate [ PMID 27918249 ], as an example of an ABCB1 substrate and treated most of the patients in the study with sertraline. (snpedia.com)
Transporter4
- AIMS: ABCB1 is a transmembrane transporter that is expressed in excretory organs (kidneys and liver), in intestine mucosa and on the blood-brain barrier. (univpm.it)
- Of note, several SNPs of ABCB1 are known and many of them affect transporter activity and/or expression. (univpm.it)
- In present study, we aimed to explore the relationship between ABCB1 transporter and the regulation of OTS964 efficacy. (biomedcentral.com)
- Phosphor-proteomics analyses uncovered S634 as a key residue of the regulatory ABCB1 linker and a very likely target of PINOID phosphorylation that determines both transporter transport activity and drug binding. (unifr.ch)
SNPs3
- T (exon 26) SNPs of ABCB1 were evaluated by PCR techniques, while plasma levels of clozapine and norclozapine were measured by HPLC in 40 men (aged, 47.6 +/- 16.6 years, median: 42 years) and 20 women (aged 40.7 +/- 11.4 years, median: 38 years) 1 month after the start of clozapine administration. (univpm.it)
- SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and their efficacy or potential for adverse side effects. (snpedia.com)
- According to a recent review [ PMID 27918249 ], ten studies reported that ABCB1 SNPs have clinical effect in depression and eight - that they do not. (snpedia.com)
Significantly4
- In a linear logistic regression model, patients with homozygous variants for one of the three ABCB1 alleles showed significantly higher short-term remission rates as compared with those of other genotypes. (uni-luebeck.de)
- Semiquantitative PCR showed that the M. guttatus ABCB1 gene copy without intron 7 had significantly lower transcript levels than the gene copy with intron 7. (biomedcentral.com)
- Because of the particular distribution of the protein, the activity of ABCB1 may significantly affect drug pharmacokinetics during absorption and distribution. (univpm.it)
- ABCB1 overexpression significantly desensitized both drug-selected and gene-transfected cells, which overexpress ABCB1, to OTS964 and that this drug resistance can be antagonized by verapamil, a known ABCB1 inhibitor. (biomedcentral.com)
Paclitaxel1
- Our results are the first to demonstrate that miR-186 may sensitize ovarian cancer cell to paclitaxel and cisplatin by targeting ABCB1 and modulating the expression of GST-π. (biomedcentral.com)
Protein expression1
- In conclusion, these data suggest that an ABCB1 variant known to alter protein expression represents an attractive candidate for future study and risk stratification in kidney transplantation. (ox.ac.uk)
Overexpression3
- In addition, overexpression of ABCB1 decreased the miR-595-overexpressing HO8910PM and SKOV-3 cell sensitivity to cisplatin. (oncotarget.com)
- Accumulating reports have suggested that acquired drug resistance is linked to ATP-binding cassette sub-family B member 1 (ABCB1) overexpression. (biomedcentral.com)
- Hence, we hypothesized that ABCB1 overexpression is possible to confer drug resistance to OTS964. (biomedcentral.com)
Variants1
- PMID 22641028 ] ABCB1 gene variants influence tolerance to selective serotonin reuptake inhibitors in a large sample of Dutch cases with major depressive disorder. (snpedia.com)
MicroRNAs1
- Recent studies have shown that microRNAs may regulate the ABCB1 gene (ATP-binding cassette, sub-family B [MDR/TAP], member 1). (biomedcentral.com)
Encodes1
- Unexpectedly, the ABCB1 (ATP-Binding Cassette Subfamily B Member 1) gene which encodes a P-glycoprotein and underlies dwarfing traits in maize ( br2 ), sorghum ( dw3 ) and pearl millet ( d2 ) displayed considerable variation in intron composition. (biomedcentral.com)
Chemotherapeutic1
- Our findings advocate further clinical investigation of combination chemotherapy of cetuximab and conventional chemotherapeutic drugs in ABCB1 overexpressing cancer patients. (oncotarget.com)
Plasma concentrations1
- CONCLUSION: c.3435CC patients require higher clozapine doses to achieve the same plasma concentrations as CT or TT patients, and ABCB1 genotyping should be considered as a novel strategy that should improve drug use. (univpm.it)
Interestingly2
- Interestingly, cetuximab decreased the cell membrane fluidity which was known to decrease the function of ABCB1. (oncotarget.com)
- Interestingly, an ABCB1 inhibitor verapamil (VPL) can re-sensitize the acquired resistance to OTS964 and restore the efficacy of OTS964 to similar level as drug-sensitive cells do. (biomedcentral.com)
Doxorubicin1
- Furthermore, cetuximab markedly increased intracellular accumulation of doxorubicin (DOX) and rhodamine 123 (Rho 123) in ABCB1-overexpressing MDR cancer cells in a concentration-dependent manner. (oncotarget.com)
Donor1
- Donor ABCB1 variant associates with increased risk for kidney allograft failure. (ox.ac.uk)
Species2
- All introns in ABCB1 underwent either a one-time loss (single loss in one lineage/species) or multiple independent losses (parallel loss in two or more lineages/species) with the majority of losses occurring within the grass family. (biomedcentral.com)
- Intron 7, the longest intron, was lost in only a single species, Mimulus guttatus , following duplication of ABCB1 . (biomedcentral.com)
Correlation1
- Dual-luciferase reporter assay was used to reveal the correlation between miR-186 and ABCB1 . (biomedcentral.com)
Interaction1
- Our special interest lies in the physical and functional interaction between the auxin exporter, ABCB1, and its regulatory interacting protein, the FKBP42, TWISTED DWARF1 (TWD1). (unifr.ch)
Contrast2
- In contrast, the structure of the closest homolog to ABCB1 , ABCB19 , remained constant in the majority of angiosperms analyzed. (biomedcentral.com)
- In contrast, ABCB1 is barely interacting with hydrophilic compounds, but is activated by hydrophobic compounds. (unibas.ch)
Cancer4
- We identified ABCB1 as a direct target gene of miR-595 in the ovarian cancer cell. (oncotarget.com)
- ABCB1 expression was upregulated in the ovarian cancer tissues and cell lines. (oncotarget.com)
- Morevoer, the expression level of ABCB1 was inversely correlated with miR-595 in the ovarian cancer tissues. (oncotarget.com)
- Fig. 7: Tepoxalin is active against ABCB1-high cancer cell lines via an ABCB1-mediated mechanism. (nature.com)
Drug3
- By means of MTT-based cell viability assay, we examined the susceptibility of OTS964 to cells overexpressed ABCB1 and found that the effectiveness of OTS964 was restricted in both drug-selected and gene-transfected cells, which overexpress ABCB1, compared to those of the corresponding parental cells (Fig. 1 A-C and Table S 1 ). (biomedcentral.com)
- Upon ABCB1 gene knockout, the cell viability curves of drug-resistant cells were overlapping with those of the parental cells, and SW620/Ad300 cells became more sensitive to OTS964 after ABCB1 knockout (Fig. 1 C-D and Table S 2 ). (biomedcentral.com)
- H ) Overview of PTX and the best-scoring pose of OTS964 in the drug binding pocket of ABCB1 protein. (biomedcentral.com)
Cells2
- The concentration-response curves and IC 50 values for OTS964 with or without a verified ABCB1 inhibitor in A ) KB-C2 and KB-3-1, B ) HEK293/ABCB1 and HEK293/pcDNA3.1, C ) SW620/Ad300 and SW620, and D ) SW620/Ad300-ABCB1ko and SW620-ABCB1ko cells. (biomedcentral.com)
- The intracellular accumulation of [ 3 H]-PTX in E ) KB-C2 and KB-3-1 and F ) HEK293/ABCB1 and HEK293/pcDNA3.1 cells after 2 h of pretreatment with vehicle, OTS964, or VPL. (biomedcentral.com)
Effects1
- E - F Effects of OTS964 on transport function mediated by ABCB1. (biomedcentral.com)
Cell1
- Ectopic expression of ABCB1 promoted the miR-595-overexpressing HO8910PM and SKOV-3 cell proliferation, colony formation and invasion. (oncotarget.com)